The compound 2-((5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-yl)thio)acetic acid (1), commonly known as Lesinurad, is described in WO 2009/070740 A2, for instance, in Example 8. Lesinurad is marketed in the United States as ZURAMPIC®, and is indicated, in combination with a xanthine oxidase inhibitor, for the treatment of hyperuricemia associated with gout. Lesinurad is also marketed in the United States as DUZALLO®, a combination with the xanthine oxidase inhibitor Allopurinol, for the treatment of hyperuricemia associated with gout.

WO 2012/092395 A2 reports the preparation of two crystalline forms of Lesinurad, which are referred to as Form 1 and Form 2. According to the disclosure of WO 2012/092395, Form 1 can undergo conversion to Form 2 and is furthermore composed of a mixture of agglomerates of plate-like crystals. Form 2 is described as a free flowing solid having lower solubility than Form 1 in certain aqueous conditions. Further, the processes used to prepare these crystalline forms include steps that are not practical for use on a commercial scale.
WO 2015/075561 A2 describes crystalline Forms III, IV, V and VI of Lesinurad, as well as crystalline Forms α, β, , and δ of Lesinurad sodium salt. Form III is identified as being anhydrous, with hygroscopicity under some conditions. However, it is prepared from acetonitrile, which is an undesirable solvent to use for a final crystallization step. Form IV is identified as a dichloromethane solvate, Form V is identified as a 2-methyltetrahydrofuran solvate, and Form VI is identified as a trichloromethane solvate. However, according to the ICH (International Conference on Harmonisation) guidance document Q3C (R5): Impurities: Guideline for Residual Solvents, dichloromethane and trichloromethane are designated as Class 2 solvents, which limits the amounts of residual solvents that are permissible in a pharmaceutical product. Notably, when a 200 mg daily dose of Lesinurad is considered, the daily amounts of dichloromethane and trichloromethane that would be administered to a patient would exceed the limits allowed under the ICH guidelines. Thus, crystalline forms containing these solvents, such as Forms IV and VI, are impractical for commercial use. The Q3C guidance designates 2-methyltetrahydrofuran as a Class 4 solvent, which is a solvent that may also be of interest to manufacturers of excipients, drug substances, or drug products but for which no adequate toxicological data on which to base a permitted daily exposure (PDE) was found. In the case of Class 4 solvents, manufacturers are required to supply justification for residual levels of these solvents in pharmaceutical products. Thus, as for Forms IV and VI, Form V, the 2-methyltetrahydrofuran solvate, is not desirable for commercial use.
CN 104557748 A discloses crystalline Forms α and β. Form α, which is reported to contain between 13.1-17.3% (by weight GC) dichloromethane, is used as in intermediate in the formation of Form β. Accordingly, both forms suffer from the requirement that dichloromethane, a chlorinated Class 2 solvent in the ICH Guidance that is a potential carcinogen, be used in the manufacturing process. As discussed, for a 200 mg dose of Lesinurad, crystal forms containing large amounts of dichloromethane exceed the allowed daily exposure for the solvent.
WO 2015/095703 A1 relates to salts of Lesinurad and co-crystal forms of Lesinurad with proline and glycolic acid. Proline is an amino acid having a primary amine group with a pKa of approximately 10.6. As a result, proline is capable of forming either a salt or co-crystal with Lesinurad, which makes it a less favoured form owing to potential regulatory complications and implications associated with the characterization of the material. Glycolic acid, on the other hand, is a corrosive substance, which can be converted in the body to the toxic metabolite oxalic acid.
Different crystalline forms of the same compound may have different packing, thermodynamic, spectroscopic, kinetic, surface and mechanical properties. For example, different crystalline forms may have different stability properties. A particular crystalline form may be more sensitive to heat, relative humidity and/or light. Alternatively or additionally, a particular crystalline form may provide more compressibility and/or density properties thereby providing more desirable characteristics for formulation and/or product manufacturing. Particular crystalline forms may also have different dissolution rates, thereby providing different pharmacokinetic parameters, which allow for specific forms to be used in order to achieve specific pharmacokinetic targets. Differences in stability may result from changes in chemical reactivity, such as differential oxidation. Such properties may provide for more suitable product qualities, such as a dosage form that is more resistant to discolouration when comprised of a specific crystalline form. Different physical properties of crystalline forms may also affect their processing. For example, a particular crystalline form may be more resistant to flow, or may be more difficult to filter and/or wash.
Although general approaches to crystalline form screening of active pharmaceutical ingredients are known, it is well established that the prediction of whether any given compound will exhibit polymorphism is not possible. Furthermore, prediction of the properties of any unknown crystalline forms, and how they will differ from other crystalline forms of the same compound, remains even more elusive (Joel Bernstein, Polymorphism in Molecular Crystals, Oxford University Press, New York, 2002, page 9).
Known crystalline forms of Lesinurad are associated with various disadvantages, such as a propensity to convert to another crystalline form, particles that agglomerate, low solubility, hygroscopicity and incorporation of toxic or questionable solvents in manufacturing processes and co-crystal formers for which no adequate safety data is available. Therefore, there exists a need for novel crystalline forms of Lesinurad for use in providing improved drug products containing Lesinurad and their manufacture.